Biotransformation of Drugs

3. Xenobiotics are chemical substances found
within an organism that are not naturally
produced by or expected to be present
within that organism.

5. Biotransformation is chemical conversion of
lipophilic xenobiotics to make them more
hydrophilic or water soluble so that they can
readily excreted by urine or bile.

6. Absorption and Distribution
Water insoluble Xenobiotic
Biotransformation
Excreted by Urine or Bile
Water soluble Xenobiotic

7. It means chemical alteration of
chemicals drugs in the body.
It affects the drug in two major ways:
• Reducing lipid solubility
• Alterations of biological activity

8. Reducing lipid solubility
• Biotransformation converts these lipid soluble
drugs to more polar and water soluble
compound that are more readily excreted by
the kidney.
• Drugs that are already water soluble are
generally excreted unchanged by the kidney.

9. Alterations of biological activity
example
Metabolite(s)
Drug
Most drugs
Inactive
Active
Codeine to
morphine
Active
Active
Enalaprill to
enalapriate
Active
Inactive
(prodrug)

10. Sites of Biotransformation
• The major site of drug metabolism is the liver
(microsomal enzyme system of hepatocytes)
Secondary organs of biotransformation
• Kidney (proximal tubule)
• Lungs (type II cells)
• GIT
• Skin
• Brain

11. Sites of Biotransformation
Intracellular:
Microsomal (present in
smooth endoplasmic
reticulum) mainly by
Cytochrome P450 enzymes
Non Microsomal
• Mitochondria
• Cytoplas
Extracellular:
plasma

12. Phases of Biotransformation
Phase I :
The most important enzyme system involved in phase I
metabolism is the Cytochrome P450 monooxygenase system

13. Cytochrome P450
Site

14. P450 IN HUMANS

15. Mechanisms of p540 catalysis

16. Phase II :

17. Drug
metabolism
Phase I
Functionalization
Phase II
Conjugation

18. Factors affecting metabolism of drugs
Physiochemical properties of the drug

19. Factors affecting metabolism of drugs
Chemical factor
Biological factor

20. Thank you for your attention